Alfonzo, who went 2-for-4, hit a two-run double off Sterling Hitchcock in a four-run fifth as the Mets overcame a 5-2 deficit.
Mike Piazza broke out of an 0-for-9 slump with an RBI single that scored Alfonzo to tie it at 5. Piazza went 3-for-4 with three RBIs.
New York, which has won two straight following a three-game losing streak, remained one-half game behind Atlanta in the NL East. The Mets rallied from a 3-0 deficit to defeat San Diego on Tuesday.
Padres outfielder Tony Gwynn left in the fifth inning with a sore left knee he aggravated sliding into third base. Gwynn, who singled in the first for his 3,007th career hit to tie Al Kaline for 20th on the career list, is listed as day-to-day.
Pat Mahomes (6-0) gave up one hit in 2 1-3 scoreless innings. Hitchcock (11-9) allowed six runs and 10 hits in 4 2-3 innings as San Diego lost its fifth straight.
The Mets broke the game open with a six-run seventh. Robin Ventura led off with his 26th homer. The Mets loaded the bases with two outs against Carlos Almanzar before Alfonzo walked on four pitches to force in Roger Cedeno, who had singled. John Olerud followed with a two-run single, and Piazza capped the inning with a single to right to score two more runs.
New York starter Octavio Dotel put the Mets in hole in the first when he threw 40 pitches and the Padres took advantage of four walks by loading the bases twice.
The Mets came back in their half to tie it at 2. Henderson led off with a single to left, moved to second on a balk by Hitchcock and scored on Alfonzo's 17th homer, which matched his career high.
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