After winning the toss and electing to bowl, India made early inroads, dismissing Afghanistan opener Rahmanullah Gurbaz for a duck in the second over before reducing their opponents to 96-5.
Captain Ibrahim Zadran anchored Afghanistan's innings with 37 off 33 balls, while a late counter-attack from Mohammad Nabi (20) and Rashid Khan (28) helped them recover to 159-8 from their 20 overs.
Reddy was the pick of India's bowlers, returning figures of 3-24.
India's chase got off to a blistering start as Samson and Abhishek Sharma put on 88 runs in just 38 balls for the opening wicket.
Rashid sparked Afghanistan's fightback by dismissing Sharma for 39 and Samson in quick succession before removing India captain Shreyas Iyer for 11 to leave the hosts on 123-3.
However, the T20 World Cup holders had enough batting depth, with Ishan Kishan and Tilak Varma adding an unbeaten 40 runs off 25 balls to guide India home. Kishan sealed victory with a boundary as India reached their target with 31 balls to spare.
India had opened the series with a commanding seven-wicket win on Sunday.
"Looking at the last match and coming into this one, we were demanding a comprehensive win and today was a good one," Iyer said.
"The journey is always going to be a roller-coaster and you have to be in equilibrium as much as possible. The more you embrace the situation, the better it gets."
India will face Afghanistan in the final T20 at the same venue on Thursday.
Iyer said the final match would offer an opportunity to give playing time to members of the squad who had sat out the first two games.
"Definitely we want all of them to get used to the wicket and get some practice, so will be a good opportunity to give a chance to the guys sitting out," he said.