Both of Favre's touchdown passes went to Donald Driver, who caught nine for 110 yards. Ahman Green, plagued by fumbling problems during the losing streak, gained 81 yards on 21 carries and also threw a touchdown pass.
Green Bay improved to 2-4, halting their lost skid in 13 years.
The Packers totaled 434 yards of offense and had the ball for almost two-thirds of the game. Detroit (3-2) managed just five first downs and picked up a total of 125 yards.
The Lions had won their previous two games. But Joey Harrington was limited to 101 passing yards while completing just 12 of 23.
Favre was 23 of 35 and had a touchdown pass for the 31st straight game, the second best total in NFL history. His 47,126 career yards are also fourth best, moving Favre ahead of Fran Tarkenton on the all-time list.