The defeat means the Poles, who were playing at home in the southern city of Chorzów, face relegation to League B of the Nations League.
Italy, oozing potential and class, created a series of chances in the second half on Sunday but lacked precision finishing until the 92nd minute.
After a corner, Cristiano Biraghi slotted the ball into the bottom right of the Polish net in the second minute of stoppage time.
Luck and a series of acrobatics by Poland goalie Wojciech Szczęsny allowed the Poles to keep a clean sheet in the first half.
Poland on Thursday lost 2-3 to Portugal in their second match of the Nations League, a sobering home defeat that exposed the sides frailties and left fans in low spirits.
The Poles in early September drew 1-1 with Italy in their first match in the group stage of the Nations League.
That game, in Bologna, was a promising debut by Jerzy Brzęczek as manager of the Polish national squad. He took over after Poland’s early exit from the World Cup in Russia.