Hornish joined Penske again in 2010. At the season-opening Daytona 500, Hornish started 26th and was involved in an early accident on the race's ninth lap; he finished 37th, completing 160 of its 208 laps. His qualifying results improved slightly during the rest of the season, with three top-fives. Hornish's only top-ten finish of the season was tenth place at the Sylvania 300 at New Hampshire Motor Speedway. He finished 29th in the standings, with 3,214 points. After the season Hornish's longtime sponsor, Mobil 1, left him and Penske for Tony Stewart and Stewart-Haas Racing. In the 2010 Nationwide Series he drove the season-ending race at Homestead-Miami for Brian Keselowski Motorsports (in conjunction with Penske) in its No. 26 Dodge Avenger, starting twelfth and finishing 21st.