Entanglement, one of the central mysteries of quantum mechanics, plays an essential role in numerous applications of quantum information theory. A natural question of both theoretical and experimental importance is whether universal entanglement detection is possible without full state tomography. In this work, we prove a no-go theorem that rules out this possibility for any non-adaptive schemes that employ single-copy measurements only. We also examine in detail a previously implemented experiment, which claimed to detect entanglement of two-qubit states via adaptive single-copy measurements without full state tomography. By performing the experiment and analyzing the data, we demonstrate that the information gathered is indeed sufficient to reconstruct the state. These results reveal a fundamental limit for single-copy measurements in entanglement detection, and provides a general framework to study the detection of other interesting properties of quantum states, such as the positivity of partial transpose and the k-symmetric extendibility.