Henderson tied Cobb's record of 2,245 runs scored when he raced around from first base on a double into the right-field corner by Ryan Klesko in the third inning. Already the major leagues' all-time leader in walks and stolen bases, Henderson was treated to a pair of standing ovations and responded with two curtain calls.
Henderson went 0-for-3 with a walk and remains three hits away from becoming the 25th member of the 3,000-hit club.
Sheffield belted a two-run homer -- his 35th -- 419 feet over the left-field wall off Padres starter Bobby Jones (8-19) to highlight a four-run first inning. Lo Duca added his 25th homer, a three-run shot to left-center, in the seventh.
Los Angeles starter Eric Gagne (6-7) allowed two runs and three hits in six innings as he recorded his first win since July 26.