Strangers in Paradise: High School! by Terry Moore
Francine and Katchoo have always been a study in contrasts. Francine is soft, chubby, and flighty, prone to fits of giddiness and a constant worrier. Katchoo is hard, lean, and dangerous, prone to fits of violence, and constantly vigilant. That these two should be best friends baffles, until you delve into their high school years.

For Francine, torture came in the forms of being a klutz, always being the odd one out, being the starry-eyed romantic when she's just a chubby girl on the fringe. Francine has a family who loves her, a mother who feeds her whenever something goes wrong, a father who spends an awful lot of time at the office, and a brother more interested in college life than his little sister.
Katchoo, on the other hand, is a self-declared outcast. She smokes, she rides a motorcycle, she is just as likely to punch you as to acknowledge you, and generally has no use for the people serving the same four-year term at puncture high. But where Francine's family provides (in their own way) comfort when the chips are down, Katchoo's family is likely to be the reason the chips are down.

Maybe it's not so surprising that these two girls find one another, and take solace in beig outcasts together.

I have heard about Moore's series but never read any before. So now I need to figure out how to read them and start from the first volume.