The issue goes on sale on Wednesday.
DC Comics co-publisher Jim Lee, who has drawn each issue of "Justice League" since its debut, said the canoodling is not a stunt or an alternate reality smooch.
"This has been in the works for some time and we certainly wouldn't have pulled the trigger on without there being great creative benefit to the liaison," he explained in an email. "Beyond the joy and sorrows of new love, there are potentially huge ramifications and dramatic ways this single relationship between these iconic characters will change the entire political and interpersonal landscape of the DC Universe."
The two characters have long formed, along with Batman, the triumvirate of DC Entertainment's heroes and are among the most powerful and best-known.
In the 1980s, the pair had a brief fling but Superman went on to marry Lois Lane. They also kissed in Frank Miller's "Dark Knight Strikes Again" a decade ago. In a 2006 epilogue to 1996's "Kingdom Come," the couple asks Bruce Wayne (aka Batman), to stand as godfather to their unborn child.
Since DC relaunched its characters and universe nearly a year ago, some of the origins have changed - Wonder Woman is now the daughter of Zeus - and the costumes have, too.
One aspect that did not survive the relaunch: Lois Lane's role as Superman's love interest. She's still around, but the two have never dated, nor are they likely to.
Geoff Johns, who writes "Justice League," is laying out a story that looks not only at the couple but the effects on others, too, Lee said.
"The way Geoff unfolds the story and the implications of two of the most powerful characters in the DCU becoming a team is something that goes beyond the question of 'What about Lois and Clark?"' Lee said.
"This is a statement to every nation and geopolitical organization in the entire DC Universe giving creative teams ample material to explore this relationship on so many different levels."