The captain and James Milner were brought on with 59 minutes on the clock at St Mary's and the scoreline finely poised at 1-1.
The duo's introduction had the desired impact as Mohamed Salah made it 2-1 before Henderson secured the three points with a well-worked goal four minutes from time.
Asked what the message from the boss was, Henderson told Liverpoolfc.com: "Make a difference.
"Use our experience and then make a difference. Help the lads, get them going because we were under a bit of pressure.
"I felt as though we did that coming on, but so did everybody else.