Boca slump to shock home defeat
Palermo, a cult figure at Boca, came on as a second-half substitute to a rousing reception. He had been out since tearing ligaments in his right knee in August.
Boca were already trailing when he came on, Diego Armani having scored on the hour.
Mauricio Sperdutti added the second with a powerful right-foot drive from outside the area in the 73rd minute to leave Newell's, coached by former Argentina international Roberto Sensini, with six points from two games in the Clausura championship.
Boca have three points.
Roberto Nanni headed an equaliser in the fourth minute of injury-time as Velez Sarsfield snatched a dramatic 1-1 draw with Argentinos Juniors.
Nestor Ortigoza had put the visitors ahead with a penalty in the 32nd minute.
Huracan also have six points after beating Racing Club 4-1 on Friday.