Thousands of feet up in the air, David Byrne looks down at the land beneath him. He sees a baseball diamond, a school and houses, restaurants and bars, "for later in the evening". He imagines the lives of men and women with whom he shares a passport (if they have passports), driving their cars down highways and clocking in and out at work. But he may as well be observing a different species. "I guess those people have fun with their neighbours and friends," he sings. Then, "I wouldn't live there if you paid me. I wouldn't live like that, no siree."

I've no idea what David Sedaris thinks of Byrne or his band, Talking Heads. But I kept being reminded of that song as I read his latest collection of autobiographical essays and skits. It captures Sedaris's particular kind of alienation, of never quite being at home among the country clubs and Costcos. It echoes his contempt for the ordinary – and often for ordinary people. This suburban kid, weedy, half Greek, gay, was always going to feel out of place in Raleigh, North Carolina. "Is this how a normal boy would swing his arms?" he wonders. "Is this how he'd laugh? Is this what he would find funny?" But this inability to be normal, at first a handicap, has become his metier. He morphed into a deadbeat artist, then a drug addict, then an improbably successful writer. His five most recent books all made the New York Times bestseller list.

Not that success has reconciled him to the world. He seems to bob around it like a bemused jellyfish, his boyfriend Hugh in tow. There are legions of fans, of course, like-minded individuals, but these are the kind who latch on to you because you make them feel less weird – less like they're the only ones who might, say, appreciate the numinous qualities of a colonoscopy.

So he carries on looking in from outside. Years of observation – he's kept a diary since 1977 – have turned him into a decent comedian. There are lines that go off like firecrackers, storing up their hilarity until the last moment, and there are the ones he lobs like little grenades amid the chaos and merriment. "Dad wants Greg Sakas to be his son instead of me, I thought" he writes in "Memory Laps", recalling the summer a swim-club rival emerged as the boy against whom he would be weighed and found wanting. Silliness here is frequently served with a side dish of regret, or disappointment, or tenderness. In "A Guy Walks into a Bar Car" Sedaris manages to distil the sense of loss that afflicts anyone who's ever had a romantic adventure offered up on a plate, and failed to tuck in.

Sincerity is at least as plentiful as cynicism. Having defined his own genre, Sedaris doesn't have to stick to the rules. In a lesson for too-clever satirists, he often fails to maintain his cool: the irony falls away to reveal, unselfconsciously, a joy at being alive. There is an essay called "Loggerheads", the best in the collection, that starts with him and Hugh swimming in Hawaii: "[We] turned to find a gigantic sea turtle coming up between us. As gentle as a cow, she was, and with a cow's dopey, almost lovesick expression on her face. That, to me, was worth the entire trip, worth my entire life, practically. For to witness majesty, to find yourself literally touched by it – isn't that what we've all been waiting for?" From this we plunge into a story of how he and his childhood friend Shaun would catch wounded animals – lizards and toads or flying squirrels that stubbornly refused to be petted, clawing "desperate and wild-eyed at the windowpane". Once they came across a clutch of baby turtles. As they sicken in a tank in his room, Sedaris goes to the local library to find out more about them. While there, he interrupts two men having sex in the toilets. They run away, "that flying-squirrel look in their eyes" and, feeling somehow implicated, he keeps it to himself. The turtles rot, of course, and Shaun's seemingly perfect family begins to unravel too. Weeks later, after his father's sudden death, they shoot BB guns together into woods at the back of the yard, imagining "something better, perhaps even majestic, waiting for us to grow into it".

There's a side to Sedaris that's less easy to like. The entertaining misanthropy of his previous books has a sharper edge here. An essay about the horrors of Chinese food, first published in the Guardian, had me squirming, as did the description of an Indian call-centre worker: "His voice had snakes in it. And dysentery. And mangoes." How would I have felt if he'd gone for Iranians? Maybe as though one of my literary idols had decided to "take a huge metaphorical dump on the culture and civilisation from whence [my] ancestors emerged", as Chinese-American columnist Jeff Yang had it.

And then there are the skits in which he abandons his own voice and becomes, in turn, "a woman, a father and a 16-year-old girl with a fake British accent". An author's note explains that they are "six brief monologues that young people might deliver before a panel of judges", though they're definitely not suitable for school. They drip with contempt for the kind of teapartying middle American who loves guns and hates gay marriage. Something about them feels unnecessarily vicious, perhaps because this category of people is so easy to lampoon. The humour curdles.

This is brave work, nevertheless. Not because his own life and those of his friends and relatives are mined for material – plenty of writers take pleasure in that. Sedaris is brave because he has no vanity at all, no compunction about revealing himself as weak and obsessive, sometimes cruel and hateful.

Luckily for him his writing also sings about how brilliantly clever, inventive and funny he is, a poet for everyone who wouldn't live the ordinary life if you paid them. Perhaps the best thing about American mass culture, however stultifying it might be, is the quality of the dissent it tends to generate: the music of David Byrne, for instance, or the peculiar thoughts of David Sedaris.