Peffer's departure marks the latest executive churn at Cadillac, which is trying to leverage its rejuvenated vehicle lineup to close the sales gap on German rivals BMW, Mercedes and Audi.
Peffer, 43, was named to Cadillac's top U.S. sales post in October 2013, from his previous job as CEO of Nissan Australia. He replaced Chase Hawkins, who was in the job just 13 months before being dismissed from GM in June 2013 for an undisclosed policy violation.
Peffer was picked by Bob Ferguson, senior vice president of global Cadillac, who in recent months has been spending much of his time in Washington, D.C., helping to steer GM's response to its ignition switch recall.
Ferguson, GM's top lobbyist before being picked by former GM CEO Dan Akerson in October 2012 to lead Cadillac, is likely to transition out of the Cadillac job and shift back to his Washington position full time, according to GM insiders.
Peffer leaves amid cooling Cadillac sales, following a year in which U.S. deliveries jumped 22 percent to 182,543 units, leading Cadillac to bill itself as the industry's "fastest-growing full-line luxury brand."
Through May, Cadillac sales slipped 2 percent, well off the pace to hit Ferguson's forecast for this year of at least 10 percent U.S. sales growth.
As Cadillac's head of U.S. sales and service, Peffer oversaw a sales organization of more than 100 employees and served as the face of the brand to Cadillac's roughly 940 dealerships.
Cadillac has been hurt by a 20 percent slide in sales of the ATS compact sedan this year through May. In an April interview, Peffer acknowledged that competition in that critical segment had stiffened with the debut of the Mercedes CLA sedan and other entries.
McNeil was Cadillac's sales chief from March 2010 until mid-2012, when he took the sales operations job and was replaced by Hawkins. Popular among dealers, McNeil also filled in as Cadillac's interim sales chief between Hawkins' departure and Peffer's arrival.
Cadillac's marketing unit also has seen executive churn.
Uwe Ellinghaus, the brand's global chief marketing officer and a former BMW executive, joined GM in January. He replaced Don Butler, the former Cadillac marketing chief who briefly was put in charge of overseas expansion before unexpectedly leaving GM last August. Butler emerged five months later as head of Ford's global connected-vehicle unit.
GM has shuffled the leadership at its other brands, too. In February, it appointed former Buick-GMC sales head Brian Sweeney as U.S. vice president of Chevrolet, in charge of sales, service and marketing. Former Vauxhall managing director Duncan Aldred replaced Sweeney as head of Buick-GMC sales, while also adding marketing duties.
Both Sweeney and Aldred report to Steve Hill, who was named GM's U.S. sales chief in January. Hill was appointed to that job by GM North America President Alan Batey, who took over that same month amid a broader executive shakeup.