The invention discloses a method and apparatus of real-time automatic calibration and compensation for beam drift. The method comprises the following steps that: after the primary collimation of a laser beam is conducted, the laser beam sequentially passes through three beam splitter prisms to be split to obtain a bunch of work beams and three bunches of monitoring beams; and the three bunches of monitoring beams are received by corresponding photoelectric sensing devices and are respectively used for monitoring energy drift and angular offset, parallel offset as well as collimation degree drift, and each parameter of the laser beam is adjusted in real time according to the obtained monitoring information. The device comprises a laser, a single-mode fiber, a collimating lens, a pyramid prism, a first beam splitter prism, a plano-convex lens, a first photoelectric sensing device, a second beam splitter prism, a second photoelectric sensing device, a third beam splitter prism, a rhombic prism, a third photoelectric sensing device, a computer and a nano-translation stage. The method and apparatus have the advantages of high adjustment accuracy, large adjustment range, fast and accurate adjustment process, the interference with each other is not generated, and the structure of the apparatus is concise.