<p>Two weeks ago, the Pittsburgh Panthers were on the cusp of a 3-0 start and a rivalry win at West Virginia, then let the game slip away in an overtime loss in Morgantown. This weekend, Pittsburgh will look to bounce back from that loss and start ACC play with a victory vs. 3-0 Louisville (12:00 p.m. ET, ESPN2).</p>
<p>The Panthers trailed 14-3 in the third quarter in Morgantown before reeling off 21 straight points to take a 24-14 lead in the fourth quarter. But two costly penalties on drives that ended in field goals meant that they left the Mountaineers with too much life, and the home team duly took advantage and rallied for a 31-24 overtime win.</p>
<p>That ended any hopes that the Panthers could be 5-0 and likely ranked entering a visit to Florida State in two weeks, but they do at least have an opportunity to be 2-0 in conference play when they travel to Tallahassee.</p>
<p>Pittsburgh will almost certainly be a firm favorite for next week’s visit from Boston College, but this week’s ACC opener vs. Louisville sees the Cardinals favored in their first road game after home wins over Eastern Kentucky, James Madison, and Bowling Green.</p>
<p>Will the Cardinals back up those odds, or will the Panthers take care of business at home? Read on for our Louisville vs. Pittsburgh prediction and best bets. Also, get the best value odds from <a href="/best-online-sportsbooks/">top online sportsbooks</a> such as <a href="https://affiliates.bettingnews.com/register/betonline/" target="_blank" rel="noopener">BetOnline</a>.</p>
<h2>Louisville vs. Pittsburgh Betting Trends</h2>
<ul>
<li>In the Jeff Brohm era, Louisville is 6-3 SU and 3-5-1 ATS in true road games.</li>
<li>The Cardinals are 18-6 SU and 12-11-1 ATS as a favorite under Brohm.</li>
<li>In those nine true road games under Brohm, the over is 6-3.</li>
<li>Pittsburgh is 19-39 SU and 28-28-2 ATS as an underdog under Pat Narduzzi, including 9-11 SU and 11-9 as a home underdog.</li>
<li>Since 2020, the over is 22-13 in Pittsburgh’s home games.</li>
</ul>
<h2>Louisville vs. Pittsburgh Prediction and Best Bets</h2>
<h3>Prediction: Pittsburgh to win</h3>
<p>This will be the first actual test of the season for Louisville’s defense, which has been stingy thus far. The Cardinals have allowed an average of 258 yards per game thus far, and they registered multiple takeaways in each of their last two games.</p>
<p>How much the Louisville defense is challenged vs. Pittsburgh will depend on two things. One is how well the Panthers’ offensive line can protect sophomore quarterback Eli Holstein. Holstein was sacked six times against West Virginia, and though he crossed the 300-yard mark for the second straight game, he completed only 59.5% of his passes, only the fourth time he has gone under 60% in his short Pitt career.</p>
<p>The other is how healthy star running back Desmond Reid will be. Reid got off to a decent start at West Virginia with 30 yards in six carries but suffered a lower-body injury on Pitt’s second drive and did not return.</p>
<p>Reid has not put up big numbers yet this season, but he is one of the nation’s top running backs and a capable receiving threat. If he can play and not be limited, Louisville’s defense will have a much more difficult time keeping Pitt’s offense in check.</p>
<p>Ultimately, as with many Pitt games, the big concern is whether the Panthers will beat themselves with penalties and mistakes. If they don’t beat themselves, they can and should win this game.</p>
<h3>Louisville vs. Pittsburgh Best Bets</h3>
<h4>1) <a href="https://affiliates.bettingnews.com/register/everygame/" target="_blank" rel="noopener">Pittsburgh ML (+165 at Everygame)</a></h4>
<p>Reid has been practicing this week, so that should mean he will be able to contribute for Pittsburgh vs. Louisville. The Cardinals allowed 190 (very meaningless) rushing yards on 29 attempts against Bowling Green last time out, so while they are a tough bunch defensively, Reid’s got the goods to get loose.</p>
<p>These two teams are not unevenly matched, and while Pat Narduzzi teams have a frustrating propensity for beating themselves and West Virginia’s sack-a-thon against Holstein does raise some concern about what Louisville’s defense could do, I typically favor taking the home team in a matchup that is not a mismatch.</p>
<p>If the Panthers are within four points, an outright win is the likely outcome, so I’m ignoring the spread and going for the straight-up win.</p>
<h4>2) <a href="https://affiliates.bettingnews.com/register/luckyrebel/" target="_blank" rel="noopener">Louisville/Pittsburgh Under 57 (-109 at Lucky Rebel)</a></h4>
<p>While I do see some points being scored, I also think the total is a few points higher than it perhaps should be.</p>
<p>Some late nerves may come into play with this pick, but I see a 27-24, 31-24, 30-27 type of game here. I’ll feel even better about it if the number moves to 58, because that would render 31-27 or 34-24 a push instead of a loss, but I’m fine with the risk at this number, especially if Louisville is without injured running backs Isaac Brown and Duke Watson, who are both dealing with lower-leg injuries.</p>
<h4>3) <a href="https://affiliates.bettingnews.com/register/bovada/" target="_blank" rel="noopener">Raphael Williams Jr. (Pittsburgh) Over 57.5 Receiving Yards (-115 at Bovada)</a></h4>
<p>After compiling 426 receiving yards in his first season at Pittsburgh, Williams is already over halfway to that total through three games this season, with 12 catches for 245 yards and three touchdowns.</p>
<p>After hauling in five passes for 81 yards and two touchdowns in a blowout win over Central Michigan, Williams had six catches for 119 yards and a score in the loss to West Virginia.</p>
<p>If Reid is active, Pittsburgh may air it out fewer times vs. Louisville than against West Virginia, but Williams should see get his share of opportunities to get this one over the line, and with catches of 45, 48, and 67 yards already on his ledger this season, he has the ability to knock it all out on one play.</p>
<h2 id="other-college-football-betting-information">Other College Football Betting Information</h2>
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