Flames coursed through a six-story hotel on Wednesday in a dense neighborhood in New Delhi, killing at least 21 people and injuring dozens more, according to the city’s fire department. The blaze appears to be the deadliest in the city in at least four years.

The Delhi fire department reported that eight crews had responded to a call received at 8:48 a.m. local time regarding the hotel, the Flourish Stay B&B, near Malviya Nagar, in the southern part of the capital.

The service said that 26 people had been rescued, with survivors sent to nearby hospitals, and that the fire had been extinguished. Speaking at a news conference, a doctor treating the injured said that eight had been put on ventilators. As of Wednesday evening, the cause of the fire was unknown; the city police and local government have opened investigations.

Istkhar Ahmad, 49, a driver who has lived in the neighborhood for 25 years, said that he saw the fire break out around 8:30 a.m.

“I saw a small fire in the guesthouse, it looked like it started in the kitchen,” he said. “Then we saw people upstairs crying, trying to break their windows.”

By the time rescue workers arrived, Mr. Ahmad said, fire had engulfed the whole building. He and other bystanders grabbed bedding and quilts from a nearby shop and arranged them below the hotel, to break the fall of those who jumped: about 10 or 12, he estimated.

There are several private hospitals on major streets around the tightly packed neighborhood, and many of their patients come from other countries. Afghans, other Central Asians and Africans sometimes travel to India for affordable treatments unavailable at home.

Relatives of hospital patients from abroad often accompany them and stay in cheap lodgings nearby. The Flourish Stay B&B is in Hauz Rani, historically a Muslim village, that has been surrounded by Delhi’s urban sprawl. Its narrow lanes are overhung with electrical and internet wiring, and packed with pharmacies and other businesses.

“How they can run such a big hotel in a residential area?” Tauseef Khan, 35, a lawyer who lives nearby, asked. “There are at least 10 such hotels in this area,” he added.

Delhi’s government requires that a double-bed occupancy room must be at least 120 square feet. Mr. Khan estimated that there were “maybe 50 to 100 people staying here, in about 30 different rooms.”

Prime Minister Narendra Modi offered condolences on social media, adding that India’s government would offer $2,000 to the next of kin of those killed in the fire and that those injured would receive more than $500 each.

A series of accidents earlier this year called attention to unsafe housing conditions in India’s capital. On May 30, a building collapsed less than a mile away from Wednesday’s fire, killing six people. Two other fires last month killed nine people in eastern Delhi and destroyed much of a furniture market in a northeastern part of the city.

The Delhi Fire Service has warned that short circuits caused by the heavy use of air-conditioning are a significant risk factor. Daily high temperatures in the capital hit an average of 103 degrees Fahrenheit through the month of May, slightly higher than usual despite unseasonal rainfall, and sometimes went as high as 114.